The identification of anatomical sexual dimorphisms in several forebrain regions of the rat has led to the general view that the sexual differentiation induced by gonadal steroids in these regions may relate to neural mechanisms that underlie sex specific reproductive functions such as copulatory behavior or gonadotropin secretion. Analysis of the anatomical relationships between sexually dimorphic nuclei in the forebrain suggests that they comprise a neural system of cell groups that develop under the influence of sex steroid hormones and are sensitive to the effects of circulating gonadal steroids in adult animals as well. An ongoing project involves defining the detailed organization of connections between sexually dimorphic regions of the forebrain known to play a role in modulating reproductive function. We are evaluating the neurotransmitter specific projections of the anteroventral periventricular nucleus (AVPv) of the rat using axonal transport methods combined with immunohistochemistry and confocal microscopy. The AVPv is located just caudal to the vascular organ of the lamina terminalis and appears to be a nodal point in neural pathways regulating gonadotropin secretion, and provides direct projections to regions that are thought to participate in regulating the release of gonadotropins. These anterograde multiple labeling studies suggest that neurons in the AVPV project directly to a subpopulation of gonadotropin releasing hormone-containing neurons, as well as to the tuberoinfundibular dopaminergic neurons in the arcuate nucleus that are thought to regulate prolactin secretion from the anterior pituitary. The AVPV also receives a dramatically sexually dimorphic projection from the principal bed nucleus of the bed nuclei of the stria terminalis, which is virtually absent in females. The development of this pathway is being evaluated in vivo and in vitro. This work has provided a sound framework for similar studies in the rhesus macaque. We are currently using a new explant culture method to study hormonal regulation of cerebral cortex development in rhesus macaques. This approach will not only allow greater experimental control, but will provide an opportunity to carry out extensive experimental comparisons not possible in vivo because of limited tissue availability.